Thursday, July 31, 2008

Some of you might recall my series of postings last year on the top Science questions. One of them was What Causes Species Diversity?. This is an important unanswered question in evolutionary biology even if it's conflated with speciation. We don't really have a good handle on what causes speciation.

That doesn't mean that we are completely ignorant. There are several candidates that, singly or in combination, account for much of what we understand about speciation and diversity. I'd like to quote Richard Dawkins from Unweaving the Rainbow since, as an admitted adaptationist, his view carries much more weight than that of a pluralist. (The reason will become apparent.) Here's how Dawkins describes the problem ...

The standard neo-Darwinian view of the evolution of diversity is that a species splits into two when two populations become sufficiently unalike that they can no longer interbreed. Often the populations begin diverging when they chance to be geographically separated. The separation means that they no longer mix their genes sexually and this permits them to evolve in different directions. The divergent evolution might be driven by natural selection (which is likely to push in different direction because of different conditions in the two geographical areas). Or it might consist of random evolutionary drift (since the two populations are not genetically held together by sexual mixing, there is nothing to stop them drifting apart). In either case, when they have evolved sufficiently far apart that they no longer interbreed even if they were geographically united again, they are defined as belonging to separate species.

Either, or both, of the two main mechanisms of evolution—natural selection and random genetic drift—can lead to speciation and diversity.

One could also argue that diversity depends ultimately on mutation. In this case, the main role of natural selection and random genetic drift is to reduce diversity by eliminating unfit and neutral alleles.

This has always been similar to my understanding of speciation and diversity. I was surprised, therefore to learn that one of my colleagues at the University of Toronto, Spencer Barrett, doesn't think random genetic drift plays a role in speciation [see Darwinism at the ROM]. Barrett is one of the featured presenters in a video at the Darwin exhibit at the Royal Ontario Museum.

In a display on the evolution/creation controversy, I copied down the following statement ...

Darwin's Theory of Evolution by Natural Selection is the only scientific explanation for the spectacular diversity of life on Earth.

So, here's the question of the day. Do you agree with that statement? Do you agree that natural selection is the only scientific explanation of diversity? Spencer Barrett seems to agree. Richard Dawkins would not agree. What do you think?1

1. If you disagree with the statement then please try and explain why it is featured so prominently in the Darwin exhibit. Is this an example of framing, or ignorance?

My how time flies. It was almost four months ago that the The Evolution Revolution opened at the Royal Ontario Museum (ROM) here in Toronto. The ROM is only ten minutes from my office so I wasn't in any particular rush to see the exhibit. After all, it wasn't going to close until August 4th.

Now August 4th is almost here and I still hadn't made the effort—until yesterday, that is. Ms. Sandwalk and I went and got a delightful dose of Charles Darwin.

For me, the most exciting exhibit was Darwin's red notebooks, especially the page with the tree and "I think" at the top of the page. It was awesome just realizing that Charles Darwin himself wrote those words 170 years ago. Ms. Sandwalk was not nearly as impressed (those messy things?). She liked the Wedgewood china representing the better side of the Darwin family.

There were lots of examples of Darwin's original collection. Mostly plants and birds and some fossils. Seeing an old photograph of the Sandwalk was another highlight.

I've heard two main criticisms of the exhibit. The first is that there's too much to read. I agree that there's a lot to read but it's mostly well written and informative. The majority of people at the exhibit were being appropriately selective in their reading. It wasn't a serious problem. The second criticism is the American slant in some of the exhibits; notably those that address the evolution/creation controversy. It was noticeable but most of the people there just took it as quaint to learn that some states want to put stickers in textbooks.

The biggest pain for me was having to watch and listen to theistic evolutionists explain—in three separate video presentations—why there's no conflict between evolution and religion. Ken Miller did an okay job but Francis Collins looks and talks like a used car salesman, in my humble opinion.

"for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria"

Joshua Lederberg (1925 - 2008) received the Nobel Prize in Physiology or Medicine for discovering that not only do bacteria have genes, they also have sex and recombination. Bacterial sex consists of passing genes from one individual to another by a method known as conjugation. The bacteria are joined by a long hollow tube [Monday's Molecule #82].

In 1958 Lederberg was only 33 years old, making him one of the youngest Nobel Laureates. He died only a few months ago, prompting comments on several blogs (e.g. Joshua Lederberg) and a special citation tribute from John Dennehy [Joshua Lederberg].

The New York Times called him one of the 2oth century's greatest scientists—an honor that would only be contested by those who don't know him. The New York Times obituary goes on to say,

Dr. Lederberg’s discovery that bacteria engage in sex created new understandings of how bacteria evolve and acquire new traits, including resistance to antibiotic drugs. A founder of the field of molecular biology, he helped lay the foundations for many biological revolutions, including biotechnology.

Dr. Lederberg moved in diverse worlds. A brilliant analyst and visionary, he led early inquiries into the possibility of computer intelligence, theorized about alien life in distant galaxies and advised American presidents for a half century. He also wrote a weekly newspaper column, “Science and Man.” His ideas were often decades ahead of the conventional wisdom.

One of the most striking features in the development of science during the past two decades is the rapid advance in the diverse fields of biology. Here the tempo of progress continues to quicken. The research contains a vast and complex material whose major portion remains the business of specialists. The observations they make in the laboratories of basic research are apparently distant from the needs of the everyday world. But again and again we discover how short the step is from these basic findings to advances in medical therapy or diagnosis that are of importance to all of us in our daily lives.

For an example we need turn only to the previous Nobel Prize in Genetics, awarded to H.J. Muller for his discovery that X-ray irradiation can change the genetic material in living organisms. The discovery was made, and the detailed analysis carried out, in a type of small fruit fly, and at the time that the prize was awarded, perhaps gave the impression that its greatest interest was in its contribution to basic principles. Now, with the era of atomic energy upon us, we all know that the genetic risks from the high-energy radiation threatening man, belong to the things I just mentioned, of vital and immediate importance to us all.

Experimental genetics is a branch of modern biology in which progress has been especially rapid. The methods and points of view of this and its allied disciplines are indispensable for many fields of medicine today. This rapidly increasing importance of experimental genetics and cell research is easily understood. The research is now reaching towards the very elements of heredity, the structures within each cell that control its life and its behavior, and thus ultimately determine the development of the whole organism. Now we begin to see what the fundamental biological processes may be. That discoveries in this field have consequences in many others is surely no surprise to any of us.

The work of all three winners of the prize lies on this plane. Their studies are concerned with the very basis of heredity and the manner in which the genes function. That hereditary characters are transmitted from parents to offspring via special elements in the ovum and spermatozoon, the so-called genes, has long been known. The organism that develops from the fertilized ovum receives certain of the parents' characters through these genes, and the genetic material in the fertilized egg, that is to say, all these genes combined, determines the development of the organism.

The cells that together constitute an organism as a rule contain a complete set of genes characteristic of the species. In ordinary cell division these are divided and subsequently distributed equally between the two daughter cells. At fertilization, the different genetic materials from two individuals unite in the fusion of the egg and the sperm. The result of the sexual reproduction is to provide offspring with genes from both of their parents. In this way, individuals with differing combinations of characters originate. And just herein lies the biologic value of the sexual process, which can be traced throughout practically the entire animal and plant kingdoms. Without the renewal such a constant recombination of characters involves, an animal or plant species would not be able to survive the struggle for existence.

The characters, which are transmitted by the genes from generation to generation, present a picture of bewildering multiplicity. This very multiplicity of the genes' effects made it difficult to attack experimentally the problem of their structure and manner of functioning; it was impossible to trace straightforward lines that could serve as a background for an experimental study.

The situation was radically changed by Beadle and Tatum, who, through a daring and astute selection of experimental material, created a possibility for a chemical attack upon the field. Circumstantial evidence pointed to a similarity of the genetic mechanisms throughout the entire plant and animal kingdoms. Beadle and Tatum selected as object for their investigations an organism with very simple structure, a bread mold, Neurospora crassa, which is far easier to work with, in many respects, than the objects usually studied in genetics. It is able to synthesize its body substances from a very simple culture medium: sugar, salts, and a growth factor. When cultures of the mold are exposed to X-ray irradiation, mutations - that is, changes in individual genes - result as they do in other organisms. By producing a large number of such mutations and by means of an analysis of the material, which should serve as a model for analytic research, Beadle and Tatum succeeded in demonstrating that the body substances are synthesized in the individual cell step by step in long chains of chemical reactions, and that genes control these processes by individually regulating definite steps in the synthesis chain. This regulation takes place through formation by the gene of special enzymes. If a gene is damaged, for example through irradiation-induced mutation, the chain is broken, the cell becomes defective - and may possibly be unable to survive. Even in the formation of comparatively simple substances the steps in the synthetic chain are many, and consequently the number of collaborating genes large. This explains simply why gene function appeared to be so impossibly complex. The discovery provides our best means of penetrating into the manner in which the genes work and has now become one of the foundations of modern genetics. Its importance extends over other fields as well, however.

Especially valuable is the possibility it affords for detailed study of the processes of chemical synthesis in the living organism. In Neurospora material it is easy by means of X-ray irradiation to produce quickly a large number of strains in which the function of different individual genes has been disturbed. By comparing these strains we are able to determine in detail how the different stages of synthesis succeed one another when the cell's substances are formed. Beadle and Tatum's technique has become one of our most important tools for the study of cell metabolism and has already yielded results of significance to various problems in the fields of medicine and general biology.

The successful results with Neurospora also provided an incentive to continued efforts to probe the basic processes further with the aid of even simpler organisms. The bacteria are even more primitive than Neurospora. The bacterial genetic mechanism was little known; many even doubted that they had one comparable with that of the higher forms of life. Tatum extended the approaches worked out in Neurospora to the bacteria. When Lederberg came to Tatum's laboratory as a young student, they discovered that different bacterial strains could be crossed to produce an offspring containing a new combination of genetic factors. This is the counterpart of the normal sexual fertilization in higher organism; it is usually considered preferable here, however, to speak of «genetic recombination». Bacterial genetics has been developed, primarily through the efforts of Lederberg and his coworkers, into an extensive research field in recent years. He also contributed further evidence that the genetic mechanism of the bacteria corresponds to that of the higher organisms. Moreover, thanks to their simple structure and extraordinarily rapid growth, bacteria provided new and excellent possibilities for a more profound study of the genetic mechanisms. Lederberg has made many contributions in this field. Particularly important is his discovery that sexual fertilization is not the only process leading to recombination of characters in bacteria. Bits of genetic material can, if they are introduced into the bacterial body, become part of the genetic material of the bacterial cell and thus change its constitution. This is usually termed «transduction», and it is the first example demonstrating that it is possible experimentally to manipulate an organism's genetic material and to introduce new genes into it and, the organism new characters. Studies in this are now being carried out in many laboratories in different parts of the world.

The transduction process and certain other related phenomena have greatly improved our means of penetrating experimentally into the basic processes of cell function and cell growth. In all probability they will also prove to have great significance in the study of the function of the higher organisms under normal and pathologic conditions. Work in this field, carried out in laboratories throughout the world, has already greatly expanded our knowledge of the basic processes in bacteriophage infection and of the mechanism of virus infection. The observations also have opened the way to a more profound understanding of certain growth problems. Certainly cancer research will be increasingly influenced by the evolution of our knowledge of the organization of the genetic material and its manner of functioning, that has been made possible by the discoveries of this year's three winners of the Nobel Prize in Physiology or Medicine.

Doctor Beadle and Doctor Tatum. In consequence of an exemplary collaboration in which each has complemented the other to unusual advantage, it has been given to you to make discoveries of fundamental importance to our understanding of the mechanism of Life's processes.

Doctor Lederberg. At first in collaboration with your co-winners of this year's Nobel Prize, and subsequently, along ever-broadening independent lines, you have made possible the advance of research to the structure of the actual genetic material.

Gentlemen. In recognition of your outstanding contributions to science the Karolinska Institute has awarded you this year's Nobel Prize in Physiology or Medicine. On behalf of the Institute I wish to extend the warmest congratulations from your colleagues on your brilliant achievements.

It is my honoured privilege now to invite you to receive your awards from the hands of His Majesty the King.

Tuesday, July 29, 2008

The newsgroup talkorigins is back online. It's been down since last Friday but I wasn't aware of the problem until Sunday. I couldn't fix it myself so I had to get in touch with our esteemed king and moderator, DIG, and that took some time.

He has now fixed the problem so post away! Fortunately, there were no serious injuries except for John Wilkins, who was forced to drink scotch [Email hiatus].

Yes, it's the old framing argument rearing its ugly head. I know, I know, we've probably said just about everything that could be said and we should just agree to disagree. Nisbet and Mooney want us to "spin" science in the interests of promoting their favorite policies. Scientists resist because that's not what science does.

Now we have a posting by Philip H. on The Intersection that makes the issue clearer than ever before. I'm sure Nisbet and Mooney are happy.

Philip H. is discussing a Washington Post article about American voters [The American Voter]. Here's what he says about the scientific aspects of the study ...

Equally interesting to me as a scientist and framer of scientific messages, is how the writer talked about the academic work she reported on. She talks about academic conclusions from a multi-year study "couched in academic understatement." My guess is the social scientists here were doing the usual, scientifically correct thing and describing their data and conclusions within the statistically appropriate confidence intervals. Probably something along the lines of: "our results appear to apply, statistically to the American population within a 95% probability. Alternately, bootstrapped ANCOVA without regression might have yielded..." That may be correct in a talk to the National Academy of Public Administration, but somehow it always leads newspaper reporters.... to wonder what the academics area really saying, and try to get "other sides" of the story. In other words - this is bad framing for an general audience. Thankfully, in this particular case, the "fairness in reporting" stchick works - and it contributes to the reporting. In the case of Creationism/Intelligent Design vs. Evolution, it doesn't.

This is a very important point, one that the "framers" have never made explicitly. The scientific reporting of information may be okay for scientists but when you're talking to non-scientists you've got to be non-scientific. The "scientifically correct" approach just won't do for the hoi-polloi.

I know, I know, scientists hate to make firm conclusions when the data do contain the possibility of error or omission. They even hate to make black and white statements when there is a really LOW probability of error. I took those courses too.

I'm so glad he took the courses. Now he knows how scientists are supposed to behave.

But this is a public policy debate. It is about how to get American voters more engaged, or if they can be more engaged. And if the truth is Americans are one or two issue voters who inherit their political allegiances like a house or a trust fund, those facts tells us something. And no one will fault the scientists for saying so directly, and with out describing the confidence interval.

It's not true that "no one will fault the scientists." I will fault the scientists for lying or distorting the scientific truth by omitting the qualifications. And I'm not alone. Many other scientists think the same way and that's why scientists are not jumping on the spin framing bandwagon (see Going Public with the Scientific Process for a better approach).

This is an old video from This Hour Has 22 Minutes. I'm sorry to be posting it now but GrrlScientist put it up on her blog and I just couldn't resist. Again, my sincere apologies to all my American friends for what Canada has done to you.

As a general rule, the magazine New Scientist does an acceptable job of covering the issues that I'm familiar with. Sure, from time to time they screw up big time, but the good articles outweigh the bad.

The July 12-18 issue has one of the big time screw-ups. There is it on the cover, "Forget Genes: The strange inheritance from your parents." The article inside is by Emma Young, an Australian writer for New Scientist who has mostly specialized in stories about space. The title of the article in the magazine is "Strange Inheritance" and the title on the website is Rewriting Darwin: The new non-genetic inheritance

HALF a century before Charles Darwin published On the Origin of Species, the French naturalist Jean-Baptiste Lamarck outlined his own theory of evolution. A cornerstone of this was the idea that characteristics acquired during an individual's lifetime can be passed on to their offspring. In its day, Lamarck's theory was generally ignored or lampooned. Then came Darwin, and Gregor Mendel's discovery of genetics. In recent years, ideas along the lines of Richard Dawkins's concept of the "selfish gene" have come to dominate discussions about heritability, and with the exception of a brief surge of interest in the late 19th and early 20th centuries, "Lamarckism" has long been consigned to the theory junkyard.

Now all that is changing. No one is arguing that Lamarck got everything right, but over the past decade it has become increasingly clear that environmental factors, such as diet or stress, can have biological consequences that are transmitted to offspring without a single change to gene sequences taking place. In fact, some biologists are already starting to consider this process as routine. However, fully accepting the idea, provocatively dubbed the "new Lamarckism", would mean a radical rewrite of modern evolutionary theory. Not surprisingly, there are some who see that as heresy. "It means the demise of the selfish-gene theory," says Eva Jablonka at Tel Aviv University, Israel. "The whole discourse about heredity and evolution will change" (see "Rewriting Darwin and Dawkins?").

Ugh.

This is, of course, nonsense. The article is all about epigenetics but it's a very broad definition of epigenetics. One that makes you cringe when you read ...

Epigenetics deals with how gene activity is regulated within a cell - which genes are switched on or off, which are dimmed and how, and when all this happens. For instance, while the cells in the liver and skin of an individual contain exactly the same DNA, their specific epigenetic settings mean the tissues look very different and do a totally different job. Likewise, different genes may be expressed in the same tissue at different stages of development and throughout life. Researchers are a long way from knowing exactly what mechanisms control all this, but they have made some headway.

Some headway? That's quite an understatement isn't it? Emma Young then goes on to describe some of that mysterious headway. Turns out that methylation of DNA, histone modification, and RNAi are the prime suspects in the upcoming paradigm shift. Who woulda guessed?

According to the New Scientist article, there are a host of scientists who are ready to abandon the gene as the unit of evolution. These include Eva Jablonka from Tel Aviv University, Israel and Russell Bonduriansky, at the University of New South Wales in Sydney, Australia. But wait. What does Richard Dawkins have to say about this?

For Bonduriansky the accumulating evidence calls for a radical rethink of how evolution works. Jablonka, too, believes that "Lamarckian" mechanisms should now be integrated into evolutionary theory, which should focus on mechanisms, rather than units, of inheritance. "This would be very significant," she says. "It would reintroduce development, in a very direct and strong sense, into heredity and hence evolution. It would mean the pre-synthesis view of evolution, which was very diverse and very rich, can return, but with molecular mechanisms attached."

That needn't necessarily mean an end to the idea of the gene as the basic unit of inheritance, or Richard Dawkins's selfish gene, according to some. "I don't think it violates the basic concept that Dawkins articulated," says Eric Richards, at Washington University in St Louis, Missouri. "Epigenetic marks can also be viewed as part of that basic unit in a more inclusive definition of a gene," he says.

What does Dawkins himself think? "The 'transgenerational' effects now being described are mildly interesting, but they cast no doubt whatsoever on the theory of the selfish gene," he says. He suggests, though, that the word "gene" should be replaced with "replicator". This selfish replicator, acting as the unit of selection, does not have to be a gene, but it does have to be replicated accurately, the occasional mutation aside. "Whether [epigenetic marks] will eventually be deemed to qualify as 'selfish replicators' will depend upon whether they are genuinely high-fidelity replicators with the capacity to go on for ever. This is important because otherwise there will be no interesting differences between those that are successful in natural selection and those that are not." If all the effects fade out within the first few generations, they cannot be said to be positively selected, Dawkins points out.

That's a relief. All epigenetic phenomena are unstable and/or reversible and Dawkins isn't buying any of this pseudoscientific nonsense about its effect on evolution. Now if we could only convince the science writers to pay more attention to the skeptics and less attention to the self-serving "revolutionaries."

I'm still struggling with the concept of epigenetics [see Epigenetics]. Most of the modern definitions are so broad that they become meaningless. It's impossible to distinguish between epigenetics and plain old regulation of gene expression.

One of my colleagues, Craig Smibert, was so annoyed by my questions about epigenetics that he pointed me to a series of articles in Nature in the hopes it would shut me up. The relevant article is Perception of Epigenetics by Adrian Bird (Bird 2007).

It's not going to help. After describing several examples like methylation and histone modifications, Bird then points out that these modifications are not necessarily stable ...

So how accurately transmitted should an epigenetic mark be? Variation due to faulty copying is compounded by current evidence that all histone modifications, as well as DNA methylation itself, can be abruptly removed during development, thereby preventing the persistence of these modifications in a heritable epigenetic sense.

In other words, an epigenetic phenomenon doesn't really need to be heritable in order to qualify as epigenetic.

Furthermore, an epigenetic phenomenon doesn't even have to be passed on to progeny to qualify.

The restrictiveness of the heritable view of epigenetics is perhaps best illustrated by considering the brain. A growing idea is that functional states of neurons, which can be stable for many years, involve epigenetic phenomena, but these states will not be transmitted to daughter cells because almost all neurons never divide.

That's not very helpful. It's beginning to look like any activation or repression of eukaryotic genes will count as epigenetics. (According to some, it doesn't have to be eukaryotes. There is epigenetic regulation in bacteria as well, Casadesús and Low (2006).)

Here's the definition ...

Given that there are several existing definitions of epigenetics, it might be felt that another is the last thing we need. Conversely, there might be a place for a view of epigenetics that keeps the sense of the prevailing usages but avoids the constraints imposed by stringently requiring heritability. The following could be a unifying definition of epigenetic events: the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states.

Does this include simple activation and repression of genes during development in the manner of control of lac operon expression? You betcha.

Bird may be thinking mostly of histone modifications and DNA methylation but he's well aware of the fact that these are often consequences, not causes, of activation and repression. He says,

For example, transcriptional activation through sequence-specific DNA-binding proteins brings in histone acetyltransferases, which then epigenetically adapt the promoter region for transcription (for histone acetyl groups, although ephemeral, would now be epigenetic).

So we're right back where we started, Craig will not be happy. Just about anything that modifies or regulates gene expression in eukaryotes (multicellular?) counts as epigenetics.

One could ask, what's the point? Why create a special word to describe regulation of gene expression in eukaryotes (and prokarotes) using mechanisms that we've known about for thirty years?

Monday, July 28, 2008

Today's molecule isn't exactly a molecule. Your task is to figure out what's going on in the photograph. Be as specific as possible using proper terminology—remember, this is a family blog.

There's a connection between today's molecule and a Nobel Prize. Sometimes I just can't identify a molecule that points to a Nobel Laureate so I have to use something else. This is going to get harder and harder as I run out of "easy" Nobel Prizes.

The first person to correctly identify what's happening in the photo and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are three ineligible candidates for this week's reward. You know who you are.

THEME:

Nobel LaureatesSend your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I may select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: The winner is Steve Matheson who knew that the photograph represented conjugating bacteria (group sex) and the Nobel Laureate is Joshua Lederberg (1958). Congratulations Steve!

While most scientists see the problem as a lack of respect for science, John examines the other side of the coin. Noting that the Sokal Affair often comes up in these discussion, John reacts to the criticism of postmodernism implicit in that reference. It's true that most scientists agree with Alan Sokal that the worst form of postmodernism is an embarrassment to all disciplines, not just the humanities. However, it's also true that humanities (e.g. English, Sociology, Psychology) have been far more lax than the sciences when it comes to intellectual rigor. In that sense, the humanities have lost respect.

John attempts to explain the good things about postmodernism. I understand his point, although I think might be protesting just a bit too much. He concludes with,

There is a cultural divide between the humanities and the sciences, but it is not a simple one. It has to do, ultimately, with respect. The division is between those who respect science, and those who respect the humanities (and the other human-related subjects, like social science, political science and so on). Yes, we in the humanities treat science like a text. This is because, as we are not doing science, we interface with that vibrant tradition via the texts of science, mostly. And we are being, as philosophers, very "meta" about science - that is, we are discussing its discussions, and reflecting upon its reflections. Textualisation is impossible to avoid, although one can correct for it. But some of us respect science. We respect it for the same reason that Locke, Hume, Kant and Mill respected science - it is where the knowledge is gathered (or made, or constructed out of data, etc.), so it is the single most important part of human cognition and social organisation to a philosopher.

Anyone who has spent much time wading through the pious, obscurantist, jargon-filled cant that now passes for 'advanced' thought in the humanities knew it was bound to happen sooner or later: some clever academic, armed with the not-so-secret passwords ('hermeneutics,' 'transgressive,' 'Lacanian,' 'hegemony,' to name but a few) would write a completely bogus paper, submit it to an au courant journal, and have it accepted . . . Sokal's piece uses all the right terms. It cites all the best people. It whacks sinners (white men, the 'real world'), applauds the virtuous (women, general metaphysical lunacy) . . . And it is complete, unadulterated bullshit – a fact that somehow escaped the attention of the high-powered editors of Social Text, who must now be experiencing that queasy sensation that afflicted the Trojans the morning after they pulled that nice big gift horse into their city.

Gary KamiyaYes, it's all about respect. However, I still think scientists are feeling more like Rodney Dangerfield1 than the average sociologist or philosopher. The way I see it, philosophers and others in the humanities often have a very narrow view of science. It's not that they treat science as just another human endeavor, which is bad enough, it's that they treat science as something that's not a part of their disciplines. This exact point is addressed in a lecture Alan Sokal gave earlier this year [What is science and why should we care?]. "Science" is not just about rocket ships and natural selection, it's a way of thinking. A way of thinking that people in the humanities would be wise to adopt. Sokal says,

At a superficial level you could say that my topic is the relation between science and society; but as I hope will become clear, my deeper theme is the importance, not so much of science, but of the scientific worldview—a concept that Ishall define more precisely in a moment, and which goes far beyond the specific disciplines that we usually think of as "science"—in humanity's collective decision making. I want to argue that clear thinking, combined with a respect for evidence—especially inconvenient and unwanted evidence that challenges our preconceptions—are of the utmost importance to the survival of the human race in the twenty-first century.

Of course, you might think that calling for clear thinking and a respect for evidence is a bit like advocating Motherhood and Aple Pie (if you'll pardon this Americanism)—and in a sense you'd be right. Hardly anyone will openly defend muddled thinking or disrespect for evidence. Rather, what people do is to surround these practices with a fog of verbiage designed to conceal from their listeners—and in most cases, I would imagine, from themselves as well—the true implications of their reasoning.

Sokal has it right, as far as I'm concerned. The war between the two cultures is not just about whether you've read Shakespeare or Einstein, it's about how you think. Either you adopt the scientific worldview that values evidence and rationality, or you practice some form of superstition. In this sense, the humanities are just a part of science and not a separate way of knowing.

Sokal emphasizes this point again and again.

I stress that my use of the term "science" is not limited to the natural sciences, but includes investigations aimed at acquiring accurate knowledge of factual matters relating to any aspect of the world by using rational empirical methods analogous to those employed in the natural sciences.

I don't think John Wilkins would agree with this perspective since it makes philosophy—and all other humanties—just a part of a scientific worldview.2

John continues with his analysis of the two cultures problem.

Scientists often do not respect humanists, either. It is a running gag that PZ or Larry Moran will tweak me and others for being mere philosophers, but the gag is that most scientists really do think philosophy is a waste of funds and office space. Likewise they think the same thing about literary studies, history, social sciences, and in fact everything that is not their own speciality. It's not hard to see this as special pleading, but if scientists want respect, they had better show some. It's not impossible: Ed Wilson and Stephen Jay Gould are just two examples of scientists who - for all their faults - respect the humanities. Nobody has the time or energy (or mental capacity) to become experts in both fields; there's barely enough time to become expert in one subspeciality of one discipline of one field); but we can respect those who do learn those limited domains even if they are not our own. This is a plea for respect too, between the analytic and continental styles of philosophy. Neither is totally stupid nor totally on track. Rather than reject the other styles, perhaps what we should do is mutually support each other to do what we do well.

For the record, I'm much closer to Gould on this issue that it appears. I have a great deal of respect for philosophy, provided that it's done correctly. I would strongly support making philosophy and the study of logic a mandatory course in every university. Similarly, there is much to be learned about human behavior—and, let's face it, we are all interested in ourselves even if we know that we are just one species out of ten million—by studying sociology, English literature, and art history. The problem isn't lack of respect for the subject matter as much as lack of respect for the way the subjects are studied.

I'd also like to point out that I'm an equal opportunity curmudgeon—the best kind, in my opinion. While I don't hesitate to point out the muddle-headedness of philosophers like Michael Ruse and Daniel Dennett who pretend to be scientists, I also don't hesitate to make fun of scientists like Ken Miller and Francis Collins who abuse science to support religion.

In the war between rationalism and superstition there are many in the humanities who are on the wrong side. But there are lots of scientists who are wrong as well. I still think that, as a general proposition, there's more respect for the humanities out there than for science. Our society is educating an entire generation of scientific illiterates who are not only unknowledgeable about basic concepts in science but, in most cases, still quite proud of their ignorance.

The next time you hear someone say that science or math is way too hard for them, you should express your sympathy by saying, "Gee, I'm sorry you're too stupid to understand these things. What can I do to help?"

2. To put it even more bluntly. All of the humanities is simply concerned with the behavior of one particular species on this planet. It's just one tiny part of life on this planet, which, in turn, is an infinitesimally small part of the universe. Those who think that the philosophy of Plato is more important than understanding evolution have their priorities all screwed up.

I can't tell you how many times I've been in the company of "intellectuals" who can discuss at great length their operatic preferences or how many novels by Gabriel García Márquez they've read, but who don't know what DNA is or which planet is closest to Earth. In many cases these "intellectuals" seem to be downright proud of the fact that they "can't do math." Scientific ignorance is not a only acceptable among this group but seems to be almost a badge of honor.

Imagine the response if one were at a cocktail party and admitted that you didn't know who Gabriel García Márquez was, and what's more, you don't care.1 The concept of two cultures, science and humanities, isn't new—it dates from the time of the scientific revolution almost 500 years ago. The conflict is almost always characterized as the lack of respect shown by humanities toward science. Here's how C.P. Snow put it in his writings on The Two Cultures.

A good many times I have been present at gatherings of people who, by the standards of the traditional culture, are thought highly educated and who have with considerable gusto been expressing their incredulity at the illiteracy of scientists. Once or twice I have been provoked and have asked the company how many of them could describe the Second Law of Thermodynamics. The response was cold: it was also negative. Yet I was asking something which is the scientific equivalent of: Have you read a work of Shakespeare's?

I now believe that if I had asked an even simpler question -- such as, What do you mean by mass, or acceleration, which is the scientific equivalent of saying, Can you read? -- not more than one in ten of the highly educated would have felt that I was speaking the same language. So the great edifice of modern physics goes up, and the majority of the cleverest people in the western world have about as much insight into it as their neolithic ancestors would have had.

Much has been written on this topic including a book by Stephen Jay Gould (The Hedgehog, the Fox, and the Magister's Pox) that has to be the most useless contribution to the debate that has ever been published. (I say this as an unabashed fan of Gould.)

The comments on both sites are interesting. They bring up related issues such as why do we have courses like "Astronomy for Dummies" and "Science for Poets" while all science majors take pretty much the same courses as the humanities students. You don't usually find examples of dumbed down philosophy courses for biologists.

What's so amazing is that Janet even has one commenter (Shawn) who's willing to defend the superiority of the humanities over the sciences. Here's part of his comment ...

As for the topic generally: it really speaks to the elitism in the hard sciences that everyone from the "science side" is more than happy (either implicitly or explicitly) to lump the soft sciences in with fine arts and literature without batting an eye. It's also rather ironic that many people on the "science side" of this debate seem to have no problem with trotting out tired cliches, culture war bugaboos, and fourth hand anecdotes to shore up their, frankly childish, arguments regarding the irrelevancy of the humanities.

Everything from ascot-ed and monocled patricians, to post-modern mandarins, to smug artsy conformists, a rouges gallery of stereotypes and cartoons presented as if it were actual evidence. But I guess what do you expect from a bunch of nerds who have no knowledge of real life. (See? It's such an easy game to play.)

Yes, of course science saves lives and makes life better, but the actual business of living, 90% of the lifespan of the overwhelming majority of humans is dominated by subjects connected to the realm of humanities. The internet is the product of science and engineering (and massive government/tax-payer funded research), but in the end it's merely a vehicle for people to conduct their lives and maybe (or maybe not) enrich their lives. Science certainly can save your life, but the humanities make it worth living.

The humanities IS civilization and civilization is the sciences' natural habitat. Science is in fact inconceivable without the humanities.

Sunday, July 27, 2008

Stephen Jay Gould is far too good a writer to have been ignored by Richard Dawkins in his book: The Oxford Book of Modern Science Writing. According to Dawkins, he and Gould "... enjoyed—or suffered—a kind of love/hate relationship on opposite sides of the Atlantic and opposite sides of several schisms in the broad church of Darwinian theory."1 Dawkins selected an essay by Gould on Charles Darwin's book on worms.

I think Gould deserves a better hearing so I've selected two excerpts that show where he differs from Dawkins. The first is from Wonderful Life (1989). Here Gould is discussing the Burgess Shale and notes that there were many diverse species, most of which have not left modern ancestors. If you represent this diversity—or disparity as Gould prefers—as a tree, it has a rapidly expanding bushiness and out of that wide base only a few branches extend upwards to modern times. This is very unlike the traditional tree that looks more like an inverted cone with steadily increasing diversity. Gould draws certain conclusions from this data—conclusions that have been widely misinterpreted. If you're going to engage in the "evolution wars" it's a good idea to get the views of your opponents right.

This inverted iconography, however interesting and radical in itself, need not imply a revised view of evolutionary predictability and direction. We can abandon the cone, and accept the inverted iconography, yet still maintain full allegiance to tradition if we adopt the following interpretation: all but a small percentage of Burgess possibilities succumbed, but the losers were chaff, and predictably doomed. Survivors won for cause—and cause includes a crucial edge in anatomical complexity and competitive ability.

But the Burgess pattern of elimination also suggests a truly radical alternative, precluded by the iconography of the cone. Suppose that winners have not prevailed for cause in the usual sense. Perhaps the grim reaper of anatomical designs is only Lady Luck in disguise. Or perhaps the actual reasons for survival do not support conventional ideas of cause as complexity, improvement, or anything at all humanward. Perhaps the rim reaper works during brief episodes of mass extinction, provoked by unpredictable envirnonmental catastrophes (often triggered by impacts of extraterrestrial bodies). Groups may prevail or die for reasons that bear no relationship to the Darwinian basis of success in normal times. Even if fishes hone their adaptations to peaks of aquatic perfection, they will all die if the ponds dry up. But grubby old Buster the Lungfish, former laughing stock of the piscine priesthood, may pull through—and not because a bunion on his great-grandfather's fin warned his ancestors about a coming comet. Buster and his kin may prevail because a feature evolved a long time ago for a different use has fortuitously permitted survival during a sudden and unpredictable change in rules. And if we are Buster's legacy, and the result of a thousand other similar happy accidents, how can we possible view our mentality as inevitable, or even probable?

We live, as our humorists proclaim, in a world of good news and bad news. The good news is that we can specify an experiment to decide between the conventional and the radical interpretations of extinction, thereby settling the most important question we can ask about the history of life. The bad news is that we can't possibly perform the experiment.

I call this experiment "replaying life's tape." You press the rewind button and, making sure you thoroughly erase everything that actually happened, go back to any time and place the past—say, to the seas of the Burgess Shale. Then let the tape run again and see if the repetition looks at all like the original. If each replay strongly resembles life's actual pathway, then we must conclude that what really happened pretty much had to occur. But suppose that the experimental versions all yield sensible results strikingly different from the actual history of life? What could we then say about the predictability of self-conscious intelligence? or of mammals? or of vertebrates? or of life on land? or simply multicellular persistence for 600 million years? (pp. 48-50)

Note the contrast between Gould's views and those of theistic evolutonists such as Ken Miller and Simon Conway Morris. Those writers emphasize that the replay of the tape of life would still produce intelligent beings with a soul. They claim that the evidence of convergence favors such a view.

The second excerpt comes from The Structure of Evolutonary Theory. Here Gould is discussing the demise of the hardened version of the Modern Synthesis. He claims that this version, entrenched in the 1950's, is no longer correct. It needs to be expanded to include other modes of evolution.

I choose this example to illustrate two things about Gould: first, the reason why he makes such a claim and, second, how he addresses his critics. The necessity of responding to other points of view is exactly what one expects from a scientist but, unfortunately, few scientists exhibit this characteristic.

Gould is referring to an article he published in Paleobiology back in 1980. In that article he quoted Ernst Mayr's definition of the Modern Synthesis2 and then pronounced it "effectively dead."

Given the furor provoked, I would probably tone down—but not change in content—the quotation that has come to haunt me in continual miscitation and misunderstanding by critics: "I have been reluctant to admit it—since beguiling is often forever—but if Mayr's characterization of the synthetic theory is accurate, then that theory, as a general proposition, is effectively dead, despite its persistence as textbook orthodoxy" (Gould, 1980). (I guess I should have written the blander and more conventional "due for a major reassessment" or "now subject to critical scrutiny and revision," rather than "effectively dead." But, as the great Persian poet said, "the moving finger writes, and having writ ..." and neither my evident piety nor obvious wit can call back the line—nor would tears serve as a good emulsifier for washing out anything I ever wrote!)

Yes, the rhetoric was too strong (if only because I should have anticipated the emotional reaction that would then preclude careful reading of what I actually said). But I will defend the content of the quotation as just and accurate. First of all, I do not claim that the synthetic theory of evolution is wrong, or headed for complete oblivion on the ashheap of history; rather, I contend that the synthesis can no longer assert full sufficiency to explain evolution at all scales (remember that my paper was published in a paleobiological journal dedicated to the studies of macroevolution). Two statements in the quotation should make this limitation clear. First of all, I advanced this opinion only with respect to a particular, but (I thought) quite authoritative, definition of the synthesis: "if Mayr's characterization of the synthetic theory is accurate." Moreover, I had quoted Mayr's definition just two paragraphs earlier. The definition begins Mayr's chapter on "species and transspecific evolution" from his 1963 classic—the definition that paleobiologists would accept as most applicable to their concerns. Mary wrote (as I explicitly quoted): "The proponents of the synthetic theory maintain that all evolution is due to the accumulation of small genetic changes, guided by natural selection, and that transspecific evolution is nothing but an extrapolation and magnification of the events that take place within populations and species."

Second, I talked about the theory being dead "as a general proposition," not dead period. In the full context of my commentary on Mayr's definition, and my qualification about death as a full generality, what is wrong with my statement? I did not proclaim the death of Darwinism, or even of the strictest form of the Modern Synthesis. I stated, for an audience interested in macroevolutionary theory, that Mayr's definition (not the extreme statement of a marginal figure, but an explicit characterization by the world's greatest expert in his most famous book)—with two restrictive claims for (1) "all evolution" due to natural selection of small genetic changes, and (2) transspecific evolution as "nothing but" the extrapolation of microevolutionary events.—must be firmly rejected if macroevolutionary theory merits any independent status, or features any phenomenology requiring causal explanation in its own domain. If we embrace Mayr's definition, then the synthesis is "effectively dead" "as a general proposition"—that is, as a theory capable of providing a full and exclusive explanation of macroevolutionary phenomena. Wouldn't most evolutionary biologists agree with my statement today?

1. It's interesting that even when describing their differences, Dawkins puts it in the context of "Darwinian theory." Anyone familiar with the conflict knows that it was really about additions to, or conflicts with, strict "Darwinism."

2. Gould discuss this again in his 1980 Science article on "Darwinism and the Expansion of Evolutionary Theory." In that article he quotes Mayr's definition of the Modern Synthesis ...

The term "evolutionary synthesis" was introduced by Julian Huxley ... to designate the general acceptance of two conclusions: gradual evolution can be explained in terms of small genetic changes ("mutations") and recombination, and the ordering of this genetic variation by natural selection: and the observed evolutionary phenomena, particularly macroevolutionary processes and speciation, can be explained in a manner that is consistent with the known genetic mechanisms.

[Image Credit: Photograph of Stephen Jay Gould by Kathy Chapman from Lara Shirvinski at the Art Science Research Laboratory, New York (Wikipedia)]

The latest issue of Tangled Bank was supposed to appear on Blue Collar Scientist but circumstances intervened1 and PZ Myers has kindly filled the gap on Pharyngula [Tangled Bank #110].

If you want to submit an article to Tangled Bank send an email message to host@tangledbank.net. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger. For some of you that's going to be a serious problem. You have to pick your best article on biology.

Friday, July 25, 2008

Douglas J. Futuyma is Distinguished Professor in the Department of Ecology and Evolution at the State University of New York at Stony Brook [Douglas Futuyma]. He is best known for his textbooks on evolution, Evolutionary Biology, beginning with the first edition in 1979. The latest version is a shorter textbook entitled Evolution (2005).

Futuyma has also published a trade book on the evolution/creation controversy. The first edition of Science on Trial: The Case for Evolution was published in 1983 and the second edition was published in 1995. Since Futuyma is a professional scientist, he meets all the qualifications for inclusion in Richard Dawkins' book: The Oxford Book of Modern Science Writing. But he is not there.

Douglas Futuyma is a brilliant textbook author. This kind of science writing is not usually recognized, but it should be. Futuyma's ability to accurately explain complex ideas is head-and-shoulders above that of most other textbook authors—no matter what their subject. I've chosen two excerpts from Evolution (2005) to illustrate this ability. You may find them familiar—that's because they have been widely quoted and paraphrased to the point where they seem trivial. Let's not forget that it is Futuyma who first began to explain evolution in this manner.

What Is Evolution?The word evolution comes from the Latin evolvere, "to unfold or unroll"—to reveal or manifest hidden potentialities. Today "evolution" has come to mean, simply, "change." It is sometimes used to describe changes in individual objects such as stars. Biological (or organic) evolution, however, is change in the properties of groups or organisms over the course of generations. The development or ONTOGENY, or individual organisms is not considered evolution: individual organisms do not evolve. Groups of organisms, which we may call populations, undergo descent with modification. Populations may become subdivided, so that several populations are derived from a common ancestral population. If different changes transpire in the several populations, the populations diverge.

The changes in populations that are considered evolutionary are those that are passed via the genetic material from one generation to the next. Biological evolution may be slight or substantial: it embraces everything from slight changes in the proportions of different forms of a gene within a population to the alterations that led from the earliest organism to dinosaurs, bees, oaks, and humans. (p. 2)

Evolution as Fact and TheoryIn The Origin of Species, Darwin propounded two major hypotheses: that organisms have descended, with modification, from common ancestors; and that the chief cause of modification is natural selection acting on hereditary variation. Darwin provided abundant evidence for descent with modification, and hundreds of thousands of observations from paleontology, geographic distributions of species, comparative anatomy, embryology, genetics, biochemistry, and molecular biology have confirmed this hypothesis since Darwin's time. Thus the hypothesis of descent with modification from common ancestors has long had the status of a scientific fact.

The explanation of how modification occurs and how ancestors gave rise to diverse descendants constitutes the theory of evolution. We now know that Darwin's hypothesis of natural selection on hereditary variation was correct, but we also know that there are more causes of evolution than Darwin realized, and that natural selection and hereditary variation themselves are more complex than he imagined. A body of ideas about the causes of evolution, including mutation, recombination, gene flow, isolation, random genetic drift, the many forms of natural selection, and other factors, constitute our current theory of evolution or "evolutionary theory." Like all theories in science, it is incomplete, for we do not yet know the causes of all of evolution, and some details may turn out to be wrong. But the main tenets of the theory are well supported, and most biologists accept them with confidence. (pp. 13-14)

I've also chosen an excerpt from Science on Trial (1995). In order to appreciate it, you will need a bit of background. The passage below comes from a chapter on "Chance and Mutation." The chapter opens with a brief description of a play by Tom Stoppard celled Rosencrantz and Guildenstern Are Dead. For those of you not intimately familiar with Shakespeare's Hamlet, Rosencrantz and Guildenstern are two minor characters who are tricked by Hamlet and end up sailing to England where, contrary to their expectations, they will be executed. Stoppard's play is about fate and inevitability.

But just as gravity and Brownian movement may both affect the motion of an airborne particle, chance and natural selection often work simultaneously, and certain evolutionary phenomena can be understood only if we take both into account. Many populations of houseflies throughout the world have evolved a resistance to DDT—an adaptation that has come about by natural selection. In some populations, however, the adaptation is provided by a dominant gene; in some by a recessive gene; in some by a number of genes, each with a small effect. The physiological mechanism by which the genes act also varies: flies can be resistant, for example, either by having developed an enzyme that degrades DDT or by having altered the cell membrane so that DDT is less able to penetrate the tissues. These are alternative adaptive mechanisms. Which one developed in a particular population must have depended on which mutations happened to be present in the population when it became exposed to DDT—and this is very much a matter of chance. Thus, chance initially determines what genetic variations will be acted on by natural selection to develop an adaptation.

When we extrapolate this principle of indeterminacy to long-term evolution, we can understand why different organisms have evolved different "solutions" to similar adaptive "problems." By chance, they had different genetic raw materials to work with. It is doubtless adaptive for male frogs to have a vocal sac that enables them to produce resonant calls that attract females. But whether a frog developed a single sac in the middle of the throat, as in the bullfrog, or a pair of sacs on either side, as in the leopard frog, may have been affected by what mutations first occurred by chance in the ancestor of each species.

If chance is a name for the unpredictable, them almost any historical event is affected by chance. Would Hamlet's mother, watching him stab Polonius through the arras, have predicted that this would be one in a chain of events leading to the death of Rosencrantz and Guildenstern? If you had been on the island of Mauritius in the mid-Tertiary, would you have predicted that the pigeons there would evolve into flightless dodos and then become extinct in the seventeenth century because they were easy prey for sailors? If you had seen a bipedal ape on the plains of Africa in the Pliocene, could you have predicted that this feature would prove crucial in the evolution of a larger brain and the development of human culture? Probably not; for in all such instances, the event that we recognize in hindsight as a "cause" might have been followed by other events leading to a different outcome. All of evolution, like all of history, seems to involve chance, in that very little of what has happened was determined from the beginning.

The mind that cannot abide uncertainty is troubled by the idea that the human species developed by "chance." But whether we evolved by chance or not depends on what the word means. We did not arise by a fortuitous aggregation of molecules, but rather by a nonrandom process—natural selection favoring some genes over others. But we are indeed a product of chance in that we were not predestined, from the beginning of the world, to come into existence. Like the extinction of the dodo, the death of Rosencrantz and Guildenstern, or the outbreak of World War I, we are a product of a history that might have been different. (pp. 146-147)

Thursday, July 24, 2008

Find a website with a correct citric acid cycle and win $1,000,000 or equivalent!NatureNews has an article on the growth of biological Wikis as a way of involving the molecular biology community in annotating genes, proteins, etc. [Molecular biology gets wikified]. I strongly support the work of Huss et al. (2008) as I described in a previous posting [A Gene Wiki].

Now Pico et al. (2008) have tried to do for metabolic pathways what Huss et al. did for genes. Unfortunately, WikiPathways isn't going to be successful for a number of reasons.

The idea is to create a Wiki for various pathways and allow the biological community to update and comment on the various entries. However, whereas Gene Wiki did the right thing by adding the human genes to Wikipedia, WikiPathways creates its own separate database. This makes it much less accessible since not only do you have to make an effort to find the Wiki, you also have to create an account to make changes.

That's not the only problem. Let's look at a familiar metabolic pathway on WikiPathways, the citric acid cycle. Right away you can see that there are no visible chemical reactions. Instead, you just see a pathway created by lines between boxes with the names of molecules. You don't even see that CO2 and reducing equivalents are produced by this pathway! That's not going to be very useful.

Contrast the WikiPathways entry with the existing entry on Wikipedia [citric acdi cycle]. The Wikipedia entry is much more useful and, as it turns out, reasonably accurate. I'd be tempted to correct the Wikipedia entry but I'm not interested in doing all the work required to make the WikiPathways entry useful.

Speaking of corrections, when I teach my biochemistry course in the winter I challenge my students to find a single website that shows the citric acid cycle correctly. By that I mean a website where every single reaction is correctly balanced and all reactants and products are shown. The Wikipedia reactions are not correct and the sum of all reactions is incorrect, although in this case the only errors are in balancing the number of hydrogen atoms. Can anyone find the mistakes? Can anyone find a website that's correct? (You can't count any website that shows a figure from my textbook and you can't count the IUBMB website (e.g., citrate synthase). (The most serious error is in getting the products of the succinate dehydrogenase reaction wrong.)

The prize for finding a correct website is seeing your name in print on Sandwalk or $1,000,000 (one million dollars), whichever I think is the most valuable.

Wednesday, July 23, 2008

Epigenetics is one of those words that means entirely different things to different people. P.Z. Myers has put up a nice description of the term on his blog [Epigenetics]. Here's how he defines epigenetics ...

Epigenetics is the study of heritable traits that are not dependent on the primary sequence of DNA.

In fairness, he then goes on to explain that this is an unsatisfactory definition. That's an understatement.

Now, as it turns out, those scientists who work on animal development employ a definition of epigenetics that looks very much like what we used to call developmental regulation of gene expression. That's why PZ can say ...

... developmental biology basically takes epigenetics entirely for granted — development is epigenetics in action! Compare an epidermal keratinocyte and a pancreatic acinar cell, and you will discover that they have exactly the same genome, and that their profound morphological, physiological, and biochemical differences are entirely the product of epigenetic modification. Development is a hierarchical process, with progressive epigenetic restriction of the fates of cells in a lineage — a dividing population of cells proceeds from totipotency to pluripotency to multipotency to a commitment to a specific cell type by heritable changes in gene expression; those cases where there is modification of the DNA, as in the immune system, are the exception.

Here's the problem. If this is epigenetics then what's the point? When I was growing up we had a perfectly good term for these phenomena—it was regulation of gene expression. Why is there a movement among animal developmental biologists to use "epigenetics" to refer to a well-understood phenomenon?

I've been bugging my colleagues today by asking them to tell me whether certain examples of gene regulation are epigenetic or not.1 The answers are mixed so I thought I'd submit the questions to Sandwalk readers. Which of the following are "epigenetic"?

Consider an E. coli cell that grows and divides for hundreds of generations in the absence of any exogenous β-galactosides (e.g. lactose). Under those conditions the lac operon is repressed and this state is heritable from generation to generation due to the presence of lac repressor.

Consider mating type in yeast. In an α cell the a gene is suppressed from generation to generation. This is heritable regulation of gene expression. All daughter cells inherit the ability to express the α gene and suppress the a gene.

During a bacteriophage infection certain genes are turned on in a definite sequence. In the simplest cases there is a set of "early" genes that are expressed as soon as the 'phage DNA enters the cell. After a few minutes the expression of the "early" genes triggers the expression of the "late" genes. Note that the "late" genes are not transcribed initially even though they are present.

Right now your major heat shock genes (e.g. Hsp70 genes) are transcriptionally silent. However, if you are stressed by heat those genes will become active and will be transcribed at a very high rate.

During oogenesis in fruit flies the bicoid gene is expressed in nurse cells and bicoid mRNA is deposited in the egg. In males, the bicoid gene is never expressed.

One of the nucleotides at an EcoR1 restriction endonuclease site in E. coli is methylated. This blocks cleavage at that site, thus protecting the bacteria from degrading its own genome. The methylation pattern is inherited from generation to generation by the action of a methylase enzyme.

Globin genes are expressed in erythroblasts but not in brain cells. During development the globin genes are activated in erythroblast stem cells because certain activator proteins are synthesized. The globin genes are not activated in any other tissues.

During development in mammalian females one of the X-chromosomes is randomly inactivated [Calico Cats]. Once this occurs the pattern is inherited in (almost) all cells that descend from the initial embryonic cell where the inactivation first occurred. The same X-chromosome is inactivated in all daughter cells.

I'm interested in two questions. First, is it possible to define epigenetics in a rigorous manner so that we can decide whether certain cases are "epigenetic" or not? Second, what, if anything, is the difference between "epigenetics" and "developmental regulation of gene expression"?

1. And they are quite annoyed about it. Many of them are avoiding me because they don't know how to answer the questions.

[Image Credit: The cartoon is from Mark Hill's website at the University of New South Wales, Australia. It appeared originally in Nature. The figure represents a different definition of "epigenetics"—one that focuses on modifications to DNA and histones.]

I mentioned that some of the Dawkins metaphors are misleading and I suggested that Climbing Mount Improbable was one example. That prompted a comment from Richard Dawkins so I replied on his website. In case anyone is interested, I'm reproducing it here.

Richard Dawkins asks,

I am interested in the suggestion that Climbing Mount Improbable might not be an ideal title.

Richard, we've been over this ground before but for the benefit of the lurkers let me explain why I think the metaphor is inappropriate.

To begin with, you use the Mt. Improbable image as a metaphor for evolution. This is misleading since evolution encompasses more than just adaptation. It would be difficult to apply the "Climbing Mt. Improbable" metaphor to the organization of our genome, for example, since it's clearly not well-designed and could never be characterized as the peak of an adaptive landscape.

But even as a metaphor for adaptation the image is less than perfect. Most readers will see the peak of Mt. Improbable as a goal of adaptation, implying that evolution somehow recognizes that there is an ultimate perfection that all organisms seek to achieve by reaching the summit. As you well know (I hope) there are very few (any?) species that are perfectly adapted to their environment. If this were true, adaptation would cease because the species resides on the summit of Mt. Improbable.

Thus, in the real world, species tend to move about in the foothills rather than attempt to scale the highest peak. As long as they are good enough to survive and reproduce that's all that's required.

Yes, some individuals within the population might acquire a mutation that makes them a little more fit but in most cases the selective advantage will be too small to make much of a difference. I don't believe there's any great pressure to get to the top of Mt. Improbable. That's why we usually don't see perfection in nature. And it explains why most organisms do not look as though they have been designed by some intelligent being. If anything the "design" looks more like a Rube Goldberg creation, and I doubt that anyone would say that those creations represent the peak of perfection.

I prefer a different view of evolution, one that emphasizes chance and accident [Evolution by Accident]. For me, the metaphor of "Climbing Mt. Improbable" is quite wrong as a metaphor of evolution.

Now, I understand that you disagree about the role of chance and accident. You say, for example, on page 326 of Climbing Mt. Improbable, "It is all the product of an unconscious Darwinian fine-tuning, whose intricate perfection we should not believe if it were not before our eyes" (referring to the evolution of figs and fig wasps). For someone who believes that such a description is characteristic of most evolution (adaptation) the "Climbing" metaphor may seem quite appropriate.

BTW, I agree with you that your case for adaptationism is much stronger in Climbing Mt. Improbable than in The Blind Watchmaker. I especially like the chapter you mention, The Museum of All Shells, where you discuss - among other things - the contrast between your view of evolution and the mutationist view. Ironically, you begin that discussion by pointing out that this is a sophisticated controversy, "... and Mount Improbable, even in its multiple-peaked version, isn't a powerful enough metaphor to explore it."

Laurence A. Moran

Larry Moran is a Professor in the Department of Biochemistry at the University of Toronto. You can contact him by looking up his email address on the University of Toronto website.

Sandwalk

The Sandwalk is the path behind the home of Charles Darwin where he used to walk every day, thinking about science. You can see the path in the woods in the upper left-hand corner of this image.

Disclaimer

Some readers of this blog may be under the impression that my personal opinions represent the official position of Canada, the Province of Ontario, the City of Toronto, the University of Toronto, the Faculty of Medicine, or the Department of Biochemistry. All of these institutions, plus every single one of my colleagues, students, friends, and relatives, want you to know that I do not speak for them. You should also know that they don't speak for me.

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Quotations

The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Quotations

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake.
Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.
Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.
Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.
Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change.
Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.
Stephen Jay Gould (1999) p.84

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is TrueI once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.